scholarly journals A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report

2021 ◽  
Author(s):  
Iris B. A. W. te Paske ◽  
◽  
José Garcia-Pelaez ◽  
Anna K. Sommer ◽  
Leslie Matalonga ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Missense Variant ◽  
Cancer Case ◽  
Diffuse Gastric Cancer ◽  
Sequencing Data ◽  
Gastric Cancer Case ◽  
Collaborative Environment ◽  
Whole Exome ◽  
Predisposing Genes ◽  
Whole Exome Sequencing Data

AbstractHereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.

scholarly journals Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Zhou ◽  
Wenyi Zhao ◽  
Jingcheng Wu ◽  
Jun Lu ◽  
Yongfeng Ding ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Somatic Mutations ◽  
Excision Repair ◽  
Sequencing Data ◽  
Driver Genes ◽  
Cell Immunotherapy ◽  
Whole Exome ◽  
Whole Exome Sequencing Data ◽  
Gastric Cancer Patients

Neoantigens are optimal tumor-specific targets for T-cell based immunotherapy, especially for patients with “undruggable” mutated driver genes. T-cell immunotherapy can be a “universal” treatment for HLA genotype patients sharing same oncogenic mutations. To identify potential neoantigens for therapy in gastric cancer, 32 gastric cancer patients were enrolled in our study. Whole exome sequencing data from these patients was processed by TSNAD software to detect cancer somatic mutations and predict neoantigens. The somatic mutations between different patients suggested a high interpatient heterogeneity. C>A and C>T substitutions are common, suggesting an active nucleotide excision repair. The number of predicted neoantigens was significantly higher in patients at stage T1a compared to in patients at T2 or T4b. Six genes (PIK3CA, FAT4, BRCA2, GNAQ, LRP1B, and PREX2) were found as recurrently mutated driver genes in our study. Combining with highly frequent HLA alleles, several neoantigens derived from six recurrently mutated genes were considered as potential targets for further immunotherapy.

scholarly journals A Comprehensive Survey of Genomic Alterations in Gastric Cancer Reveals Recurrent Neoantigens as Potential Therapeutic Targets

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Chen ◽  
Qiming Zhou ◽  
Riping Wu ◽  
Bo Li ◽  
Qiang Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Somatic Mutations ◽  
Sequencing Data ◽  
Cell Based Therapy ◽  
Public Resource ◽  
Whole Exome ◽  
Genomic Landscape ◽  
Whole Exome Sequencing Data ◽  
Comprehensive Survey ◽  
Cancer Types

Immunotherapy directed against cancer-specific neoantigens derived from non-silent mutants is a promising individualized strategy for cancer treatment. Neoantigens shared across patients could be used as a public resource for developing T cell-based therapy. To identify potential public neoantigens for therapy in gastric cancer (GC), 74 GC patients were enrolled in this study. Combined with the TCGA cohort and other published studies, whole exome sequencing data from 942 GC patients were used to detect somatic mutations and predict neoantigens shared by GC patients. The mutations pattern between our study and the TCGA cohort is comparable, and C > T is the most common substitution. The number of neoantigens was significantly higher in older patients (age ≥60) compared to younger patients (age <60), both in this study and the TCGA cohort. Recurrent neoantigens were found in eight genes (TP53, PIK3CA, PGM5, ERBB3, C6, TRIM49C, OR4C16, and KRAS) in this study. The neoantigen-associated mutations PIK3CA (p.H1047R) and TP53 (p.R175H) are common across several cancer types, indicating their potential usage. Overall, our study illustrates a comprehensive genomic landscape of GC and provides the recurrent neoantigens to facilitate further immunotherapy.

scholarly journals Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ryan S. Dhindsa ◽  
◽  
Johan Mattsson ◽  
Abhishek Nag ◽  
Quanli Wang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Unmet Need ◽  
Missense Variant ◽  
Mitotic Checkpoint ◽  
Sequencing Data ◽  
Whole Exome ◽  
Novel Association ◽  
Whole Exome Sequencing Data ◽  
Substantial Progress

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses. Our variant-level analysis revealed a novel association between a rare missense variant in SPDL1 and IPF (NM_017785.5:g.169588475 G > A p.Arg20Gln; p = 2.4 × 10−7, odds ratio = 2.87, 95% confidence interval: 2.03–4.07). This signal was independently replicated in the FinnGen cohort, which contains 1028 cases and 196,986 controls (combined p = 2.2 × 10−20), firmly associating this variant as an IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. To the best of our knowledge, these results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.

scholarly journals Biallelic novel mutations of the COL27A1 gene in a patient with Steel syndrome

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jong Seop Kim ◽  
Hyoungseok Jeon ◽  
Hyeran Lee ◽  
Jung Min Ko ◽  
Yonghwan Kim ◽  
...  
Keyword(s):  
Hip Dysplasia ◽  
Large Deletion ◽  
Compound Heterozygous ◽  
Radial Head Dislocation ◽  
Sequencing Data ◽  
Novel Mutations ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data ◽  
Carpal Coalition

AbstractAn 11-year-old Korean boy presented with short stature, hip dysplasia, radial head dislocation, carpal coalition, genu valgum, and fixed patellar dislocation and was clinically diagnosed with Steel syndrome. Scrutinizing the trio whole-exome sequencing data revealed novel compound heterozygous mutations of COL27A1 (c.[4229_4233dup]; [3718_5436del], p.[Gly1412Argfs*157];[Gly1240_Lys1812del]) in the proband, which were inherited from heterozygous parents. The maternal mutation was a large deletion encompassing exons 38–60, which was challenging to detect.

scholarly journals Long runs of homozygosity are associated with Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sonia Moreno-Grau ◽  
◽  
Maria Victoria Fernández ◽  
Itziar de Rojas ◽  
Pablo Garcia-González ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
European Ancestry ◽  
Runs Of Homozygosity ◽  
Sequencing Data ◽  
Outbred Population ◽  
Whole Exome ◽  
Whole Exome Sequencing Data ◽  
Outbred Populations ◽  
Recessive Effects

AbstractLong runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.

scholarly journals Choroid Plexus Metastasis from Gastric Cancer —Case Report—

1994 ◽  
Vol 34 (3) ◽  
pp. 183-186 ◽  
Author(s):  
Hiromichi NAKABAYASHI ◽  
Keiji MURATA ◽  
Masakazu SAKAGUCHI ◽  
Kazuhiro NAKAJIMA ◽  
Junsuke KATSUYAMA
Keyword(s):  
Gastric Cancer ◽  
Case Report ◽  
Choroid Plexus ◽  
Cancer Case ◽  
Gastric Cancer Case

scholarly journals A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Jennifer D. Hintzsche ◽  
William A. Robinson ◽  
Aik Choon Tan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sequencing Data ◽  
Disease Treatment ◽  
Computational Tools ◽  
Whole Exome ◽  
Data Production ◽  
Whole Exome Sequencing Data ◽  
Computationally Intensive ◽  
Generation Technology

Whole Exome Sequencing (WES) is the application of the next-generation technology to determine the variations in the exome and is becoming a standard approach in studying genetic variants in diseases. Understanding the exomes of individuals at single base resolution allows the identification of actionable mutations for disease treatment and management. WES technologies have shifted the bottleneck in experimental data production to computationally intensive informatics-based data analysis. Novel computational tools and methods have been developed to analyze and interpret WES data. Here, we review some of the current tools that are being used to analyze WES data. These tools range from the alignment of raw sequencing reads all the way to linking variants to actionable therapeutics. Strengths and weaknesses of each tool are discussed for the purpose of helping researchers make more informative decisions on selecting the best tools to analyze their WES data.

scholarly journals An aromatase inhibitor (AI) has led to long-term remission in a gastric cancer case with bilateral breast cancers

2015 ◽  
Vol 26 ◽  
pp. vii128 ◽  
Author(s):  
Hiroshi Tsukuda ◽  
Takayo Ota ◽  
Tomohiro Suzumura ◽  
Yoshikazu Hasegawa ◽  
Masahiro Fukuoka
Keyword(s):  
Gastric Cancer ◽  
Aromatase Inhibitor ◽  
Cancer Case ◽  
Breast Cancers ◽  
Gastric Cancer Case
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